The objective of this renewal are to continue our studies of renal hypertension in pregnancy, with major emphasis on the following: 1) fetal hemodynamic and metabolic effects of maternal renal hypertension; 2) role of autonomic nervous system in observed maternal hemodynamic changes of hypertension; 3) effects of intra and extravascular fluid volume changes on pregnant hypertensive pathophysiology and plasma renin activity; 4) effects of various treatment modalities such as antihypertensives and diuretics; and 5) complete studies on effects of renal hypertension on maternal cardiac output and blood volume. Pregnant ewes chronically instrumented for determination of cardiac output or utero-placental blood flow by electromagnetic flow transducers will be used. Renal hypertension is induced by right renal artery constriction for a two-kidney model and contralateral nephrectomy for a one-kidney model. In the fetal studies, the renal model will be prepared but not constructed prior to chronic fetal instrumentation for determination of: 1) umbilical blood flow; 2) arterial pressure; 3) heart rate; 4) umbilical venous pressure; 5) blood gases; and 6) oxygen consumption. Following baseline fetal data, maternal hypertension will be induced by renal artery constriction and fetal hemodynamic effects observed. Activity and sensitivity of the maternal autonomic nervous system will be tested in normotensive and hypertensive pregnant sheep. Dose-response curves and the ED50 to the various autonomic agonists administered, both directly into the uteroplacental circulation and systemically, will be carried out weekly. In addition, autonomic tone will be evaluated by systemic administration of specific blockers. The effects upon the response to these agents will be compared before and after hypertension, and intravascular and extracellular fluid volume changes in the same animals.